2007 Grant - Baudry

SOD/Catalase Mimetics for the Treatment of Alzheimer's Disease

2007 Investigator-Initiated Research Grant

Highly reactive chemicals called reactive oxygen species (ROS) are believed to play a role in both normal aging and in the neurodegeneration seen in diseases such as Parkinson's and Alzheimer's. ROS cause toxicity by reacting with and inhibiting the normal function of essential molecules such as proteins and DNA. Reducing the amount of ROS may be a viable means of preventing or slowing the progression of neurodegenerative diseases.

Michel Baudry, Ph.D., and colleagues propose to test a type of ROS inhibitor called salen-manganese complexes. These chemicals mimic the action of two natural ROS scavenger enzymes called superoxide dismutase (SOD) and catalase. The researchers have shown that salen-manganese compounds can penetrate the brain and even get into the mitochondria within cells. Mitochondria are tiny, sub-cellular powerhouses that provide cells with energy. They are also the principle producers of reactive oxygen. The researchers showed that in normal mice salen-manganese complexes can reverse age-related decline in cognitive ability. Now, they plan to test the same complexes in mouse models of Alzheimer's disease.

The researchers will use a specially engineered mouse that mimics two of the key pathological hallmarks of Alzheimer's, beta-amyloid plaques and neurofibrillary tangles. Baudry and colleagues will treat mice prior to onset of pathology to test if the compounds can delay the onset of disease and after pathology is evident to see if the compounds can slow or halt the disease once it is in progress. These studies will be used to evaluate whether salen-manganese compounds may be worth pursuing as potential therapeutics for Alzheimer's disease.